JOPLING Chris

Research subject

Heart disease has now become one of the most common causes of fatality. Indeed, many European countries report that heart disease is the number one cause of death and disability. Although adult mammals are unable to significantly regenerate their heart, this is not the case for a number of other vertebrate species. In particular, zebrafish are able to fully regenerate their heart following amputation of up to 20% of the ventricle. Previously we developed the Cre/tamoxifen system for use in zebrafish and were able to lineage trace cardiomyocytes during regeneration. We found that soon after amputation, cardiomyocytes dedifferentiate and proliferate to regenerate the missing tissue, furthermore this process did not involve stem/progenitor cells. More recently, identical results have also been obtained in neonatal mice, indicating that mammals possess the potential to regenerate their heart in a similar manner to zebrafish. Our main objective is to identify genes which regulate myocardial regeneration in zebrafish and subsequently test these in mammals.

To determine suitable target genes, we will use the substantial microarray data generated from studying heart regeneration in zebrafish. To further refine the selection of candidates from the microarray data, we will target genes that are associated with specific processes that we have identified as being important for zebrafish heart regeneration. Once candidates have been selected and confirmed in our zebrafish model system we will begin testing these in vitro in mammalian cardiomyocytes before creating transgenic mouse models to determine whether they are capable of inducing myocardial regeneration following cardiac ischemia in mammals